IGHV and TP53 Status in Choosing Fixed-Duration vs Continuous Therapy

Danielle M. Brander, MD, of Duke University School of Medicine, notes that long-term CLL14 follow-up in chronic lymphocytic leukemia (CLL) showed a median progression-free survival of about 76 months with venetoclax plus obinutuzumab overall but roughly 64 months in unmutated IGHV disease and 49 to 50 months with TP53 aberrations. She asks which biomarkers drive selection among venetoclax plus obinutuzumab, the Bruton tyrosine kinase (BTK) inhibitor plus venetoclax doublet, and continuous BTK inhibitor therapy. Marc J. Braunstein, MD, PhD, of NYU Grossman Long Island School of Medicine, favors continuous therapy for unmutated IGHV and TP53-aberrant disease, either single-agent acalabrutinib or zanubrutinib or a BTK inhibitor plus an anti-CD20 antibody, since TP53-mutated patients had less benefit in CLL14 and were excluded from AMPLIFY. He expects measurable residual disease testing may eventually guide treatment withdrawal but considers these patients an unmet need. Both stress biomarker testing outside trials.